Background: Fabry disease (FD) is an X-linked inborn error of lysosomal storage disorder, a deficiency in lysosomal hydrolase α-galactosidase A activity due to pathogenic variants in the GLA gene. Accumulation of globotriaosylceramide in multiple organs contributes to end-stage kidney disease, heart failure, and cerebrovascular accidents.
Methods: We began the FD screening program by involving male patients older than 20 years of age who were on chronic dialysis, had a post-kidney transplantation, and were part of the Pre-End Stage Renal Disease Program in our hospital. α-galactosidase A activity was detected through an initial dried blood spots screen assay, followed by levels of lyso-globotriaosylceramide and sequencing of the GLA gene when screening patients with suspected FD to confirm their diagnosis.
Results: A total of 1812 patients had been FD screened, with the prevalence of FD being approximately 0.16 % (3/1812) up until June 2022. Interestingly, we confirmed a family cluster (2 sons and their mother) of having the c.936+919G>A mutation (designated GLA IVS4) with hypertrophic cardiomyopathy in Taiwan and another with the mutation c.644A>G (p.Asn215Ser), a more common later-onset variant reported in people of European or North American descent. Two patients were confirmed with cardiomyopathy through a cardiac biopsy, with their cardiac function later reversed after enzyme replacement therapy.
Conclusions: The FD screening test detects chronic kidney disease due to an unknown etiology and prevents other organ complications. Early detection of FD is crucial for reversing target organ damage with enzyme replacement therapy.
Copyright © 2023. Published by Elsevier Inc.